title: The novel anti-migraine compound zolmitriptan (Zomig 311C90) has no clinically significant interactions with paracetamol or metoclopramide.
abstract: OBJECTIVE
  This study investigated potential pharmacokinetic or pharmacodynamic interactions between the novel anti-migraine compound zolmitriptan (Zomig, formerly 311C90) and paracetamol and/or metoclopramide.
  
  
  METHODS
  In an open-label, randomised, crossover study, 15 healthy volunteers received single oral doses of 10 mg zolmitriptan alone, 1 g paracetamol alone, 10 mg zolmitriptan + 1 g paracetamol, 10 mg zolmitriptan + 10 mg metoclopramide or 10 mg zolmitriptan + 1 g paracetamol + 10 mg metoclopramide on five separate occasions.
  
  
  RESULTS
  Metoclopramide had no significant effects on the pharmacokinetics of zolmitriptan or the active zolmitriptan metabolite 183C91, nor did it affect interactions between zolmitriptan and paracetamol. Paracetamol marginally increased the maximum plasma concentration (Cmax) (11%) and the area under the curve (AUC) (11%) and reduced the renal clearance of zolmitriptan (9%); similar small effects were seen on 183C91. The AUC, Cmax and half-life of paracetamol were reduced by concomitant zolmitriptan (by 11%, 31% and 8%, respectively), whilst the mean residence time showed a small increase (+0.7 h). There was a trend towards a transient increase in blood pressure following all regimens containing zolmitriptan; this effect was small, was consistent between all zolmitriptan regimens as well as with previous studies, and was considered to be clinically insignificant. Zolmitriptan was well tolerated after all treatment regimens.
  
  
  CONCLUSIONS
  Concomitant administration of zolmitriptan and paracetamol resulted in a slight increase in bioavailability of zolmitriptan and a reduced rate and extent of paracetamol absorption. These findings are considered to be of no clinical significance and there is no reason to avoid concomitant administration of paracetamol and/or metoclopramide with zolmitriptan.
authors.affiliation: Glaxo Wellcome Research and Development, Greenford, Middlesex, UK.
authors.forename: E J
authors.initials: EJ
authors.lastname: Seaber
authors.forename: G
authors.initials: G
authors.lastname: Ridout
authors.forename: G
authors.initials: G
authors.lastname: Layton
authors.forename: J
authors.initials: J
authors.lastname: Posner
authors.forename: R W
authors.initials: RW
authors.lastname: Peck
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D008881:Migraine Disorders / Q000188:drug therapy*; D010080:Oxazoles / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D023303:Oxazolidinones; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics*; D014363:Tryptamines
chemical_list: D010080:Oxazoles; D023303:Oxazolidinones; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C089750:zolmitriptan; D000082:Acetaminophen; D008787:Metoclopramide